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Clin Cancer Res. 2013 Oct 15;19(20):5552-6. doi: 10.1158/1078-0432.CCR-13-0518. Epub 2013 Aug 13.

Pertuzumab: optimizing HER2 blockade.

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1
Authors' Affiliation: Dana-Farber Cancer Institute, Boston, Massachusetts.

Abstract

Pertuzumab has been approved by the U.S. Food and Drug Administration for use in combination with trastuzumab and docetaxel for the first-line treatment of patients with advanced HER2-positive (HER2(+)) breast cancer. Pertuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2 and inhibits heterodimerization of HER2 with other HER family members, including EGF receptor (EGFR), HER3, and HER4. The HER2-HER3 heterodimer is a robust activator of phosphoinositide 3-kinase (PI3K) pathway signaling and functions as the most transforming and mitogenic of the receptor complexes formed by the HER family of proteins; thus, blockade of HER2-HER3 likely represents the most relevant action of pertuzumab. In the seminal phase III study, patients with HER2(+) metastatic breast cancer were randomized to receive trastuzumab and docetaxel, with or without pertuzumab: Addition of pertuzumab significantly prolonged progression-free survival with an increase of 6.1 months (12.4 vs. 18.5 months, respectively). In a subsequent analysis with 30 months of median follow-up, pertuzumab conferred a 34% reduction in the risk of mortality. Here, we review the mechanism of action of pertuzumab, the rationale for combining it with trastuzumab/pertuzumab, clinical data, and future directions for this work.

PMID:
23942091
DOI:
10.1158/1078-0432.CCR-13-0518
[Indexed for MEDLINE]
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